NSABP P-1 (Breast Cancer Prevention Trial): What the Breast Cancer Trial Found

A drug given to people who did not have cancer

Tamoxifen was already established as a treatment. Doctors had noticed something in the treatment data: women taking it for a cancer in one breast developed fewer cancers in the other one.

That observation raised a much larger question. If the drug prevented a second cancer, could it prevent a first?

NSABP P-1 set out to answer that by giving a drug, with real side effects, to more than thirteen thousand healthy women. It remains one of the most consequential prevention trials ever run, and one of the most instructive about what prevention costs.

Trial at a glance

Field	Detail
Trial	NSABP P-1, the Breast Cancer Prevention Trial
Reported	1998
Design	Randomized, placebo-controlled prevention trial
Participants	13,388 women at increased risk
Comparison	Tamoxifen 20 mg a day for five years, vs placebo
Group sizes	6,681 tamoxifen, 6,707 placebo
Main measure	Breast cancer incidence

This records the trial design. Tamoxifen for prevention is a conversation to have with your own doctor, who decides whether and how much.

Who was eligible

Women qualified in one of three ways: being 60 or older; being 35 to 59 with a five-year predicted breast cancer risk of at least 1.66% by the Gail model, a calculator that combines age, family history, reproductive history, and biopsy results; or having a history of lobular carcinoma in situ, an abnormality found on biopsy that signals raised risk.

None of them had breast cancer.

What the trial found

Tamoxifen cut the risk of invasive breast cancer by 49%, with a two-sided p value below 0.00001.

The absolute figures matter more than the percentage. Over 69 months of follow-up, 43.4 women per 1,000 on placebo developed invasive breast cancer, against 22.0 per 1,000 on tamoxifen. That is about 21 fewer cancers for every 1,000 women who took the drug for five years — and, read the other way, about 979 women per 1,000 who took it and would not have developed a cancer anyway.

Non-invasive breast cancer fell by 50%, with p<0.002.

The protection was specific. Estrogen receptor-positive tumors fell by 69%. Estrogen receptor-negative tumors were no less common at all. Tamoxifen works by blocking estrogen's effect on breast tissue, so a cancer that does not depend on estrogen is untouched.

Benefit appeared across ages: a 44% reduction in women aged 49 or younger, 51% in those 50 to 59, and 55% in those 60 and over. It was larger in the highest-risk subgroups — 56% in women with a history of lobular carcinoma in situ, and 86% in those with atypical hyperplasia.

There was a bonus finding: fewer fractures of the hip, wrist, and spine.

The harms, stated plainly

Endometrial cancer — cancer of the lining of the womb — was 2.5 times more likely on tamoxifen, with a risk ratio of 2.53 and a 95% confidence interval of 1.35 to 4.97. The report notes that all endometrial cancers in the tamoxifen group were stage I, and that no endometrial cancer deaths had occurred in that group.

Stroke, pulmonary embolism, and deep vein thrombosis were all raised. Critically, these harms fell almost entirely on women aged 50 and over — the same women who stood to gain the most from the prevention side.

The rate of ischemic heart disease was unchanged. No increase was seen in liver, colon, rectal, or ovarian cancers.

When to get checked

A prevention drug is one lever, and it is not the main one. See a clinician about any of these regardless of your risk score:

• A new lump or thickened area in a breast or armpit that does not come and go with your cycle.
• Skin over the breast that dimples, puckers, or thickens.
• A nipple that has newly turned inward, or a rash or crusting on it.
• Discharge from one nipple, especially if bloody and without squeezing.
• A breast that becomes red, hot, and swollen and does not settle on antibiotics.

And if you are taking tamoxifen, report any vaginal bleeding after menopause, and any calf swelling, chest pain, or sudden breathlessness, the same day.

What this does not mean

• It reduced the number of cancers, not the number of deaths. A mortality benefit was not shown at this follow-up, which had a median of about 55 months.
• There is no protection at all against estrogen receptor-negative breast cancer, which includes many of the most aggressive tumors.
• The serious harms concentrate in women 50 and over, which is precisely where the benefit concentrates too. The decision is a trade, not a free gain.
• Eligibility was defined by a risk model. A Gail score is a population estimate applied to one person, and it does not include everything now known to matter.
• Uptake of preventive tamoxifen has always been low. Many women offered it decide the trade is not worth it, and that is a reasonable reading of the same numbers.

Questions worth asking

• What is my estimated risk, by which model, and what does that number actually mean?
• Given my age and history, how do the benefits and the clot and endometrial risks compare for me?
• What would monitoring look like if I took it, and what would make me stop?

Our guides to breast cancer and questions to ask about a clinical trial cover the background. For scale: SEER estimates about 321,910 new female breast cancers in the United States in 2026, with a median age at diagnosis of 64.

Sources

• J Natl Cancer Inst 1998: Tamoxifen for prevention of breast cancer — NSABP P-1 Study, PMID 9747868 — record retrieved via NCBI eutils
• NCI PDQ: Breast Cancer Treatment (Health Professional Version)
• NCI SEER Cancer Stat Facts: Female Breast Cancer

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

Cancer Explained is published by the National Cancer Information Foundation. It is not medical advice and does not suggest a test or treatment.

See an error, old source, or unclear wording? Tell us.